mutLBSgeneDB |
Gene summary for HCN4 |
Gene summary |
Basic gene Info. | Gene symbol | HCN4 |
Gene name | hyperpolarization activated cyclic nucleotide-gated potassium channel 4 | |
Synonyms | SSS2 | |
Cytomap | UCSC genome browser: 15q24.1 | |
Type of gene | protein-coding | |
RefGenes | NM_005477.2, | |
Description | hyperpolarization activated cyclic nucleotide-gated cation channel 4potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 | |
Modification date | 20141219 | |
dbXrefs | MIM : 605206 | |
HGNC : HGNC | ||
Ensembl : ENSG00000138622 | ||
HPRD : 09240 | ||
Vega : OTTHUMG00000137563 | ||
Protein | UniProt: Q9Y3Q4 go to UniProt's Cross Reference DB Table | |
Expression | CleanEX: HS_HCN4 | |
BioGPS: 10021 | ||
Pathway | NCI Pathway Interaction Database: HCN4 | |
KEGG: HCN4 | ||
REACTOME: HCN4 | ||
Pathway Commons: HCN4 | ||
Context | iHOP: HCN4 | |
ligand binding site mutation search in PubMed: HCN4 | ||
UCL Cancer Institute: HCN4 | ||
Assigned class in mutLBSgeneDB | A: This gene has a literature evidence and it belongs to targetable_mutLBSgenes. | |
References showing study about ligand binding site mutation for HCN4. | 1. "Xu X, Marni F, Wu S, Su Z, Musayev F, Shrestha S, Xie C, Gao W, Liu Q, Zhou L. Local and global interpretations of a disease-causing mutation near the ligand entry path in hyperpolarization-activated cAMP-gated channel. Structure. 2012 Dec 5;20(12):2116-23. doi: 10.1016/j.str.2012.09.017. Epub 2012 Oct 25. PubMed PMID: 23103389." 23103389 |
Gene ontology having evidence of Inferred from Direct Assay (IDA) from Entrez |
GO ID | GO Term | PubMed ID | GO:0071320 | cellular response to cAMP | 16407510 | GO:0071321 | cellular response to cGMP | 22748890 | GO:0071805 | potassium ion transmembrane transport | 16407510 |
Top |
Ligand binding site mutations for HCN4 |
Lollipop-style diagram of mutations at LBS in amino-acid sequence. We represented ligand binding site mutations only. (You can see big image via clicking.) : non-synonymous mutation on LBS, Circle size denotes number of samples. |
Cancer type specific mutLBS sorted by frequency |
LBS | AAchange of nsSNV | Cancer type | # samples | L708 | A707G | BLCA | 1 | R669 | R669H | COAD | 1 | R669 | R668Q | COAD | 1 | F613 | E614Q | LUAD | 1 | F613 | R612H | LUAD | 1 | R713 | R713H | LUAD | 1 | R713 | D712E | LUAD | 1 | F564,E566 | D565V | STAD | 1 |
cf) Cancer type abbreviation. BLCA: Bladder urothelial carcinoma, BRCA: Breast invasive carcinoma, CESC: Cervical squamous cell carcinoma and endocervical adenocarcinoma, COAD: Colon adenocarcinoma, GBM: Glioblastoma multiforme, LGG: Brain lower grade glioma, HNSC: Head and neck squamous cell carcinoma, KICH: Kidney chromophobe, KIRC: Kidney renal clear cell carcinoma, KIRP: Kidney renal papillary cell carcinoma, LAML: Acute myeloid leukemia, LUAD: Lung adenocarcinoma, LUSC: Lung squamous cell carcinoma, OV: Ovarian serous cystadenocarcinoma, PAAD: Pancreatic adenocarcinoma, PRAD: Prostate adenocarcinoma, SKCM: Skin cutaneous melanoma, STAD: Stomach adenocarcinoma, THCA: Thyroid carcinoma, UCEC: Uterine corpus endometrial carcinoma. |
Top |
Protein structure related information for HCN4 |
Relative protein structure stability change (ΔΔE) using Mupro 1.1 Mupro score denotes assessment of the effect of mutations on thermodynamic stability. (ΔΔE<0: mutation decreases stability, ΔΔE>0: mutation increases stability) |
: nsSNV at non-LBS: nsSNV at LBS |
nsSNVs sorted by the relative stability change of protein structure by each mutation Blue: mutations of positive stability change. and red : the most recurrent mutation for this gene. |
LBS | AAchange of nsSNV | Relative stability change | F613 | R612H | -1.4972034 | F613 | E614Q | -1.3270697 | R713 | R713H | -1.3267193 | R669 | R668Q | -1.2690316 | L708 | A707G | -0.87430219 | R669 | R669H | -0.49379184 | F564 | D565V | -0.32419279 | E566 | D565V | -0.32419279 | R713 | D712E | -0.30537518 |
(MuPro1.1: Jianlin Cheng et al., Prediction of Protein Stability Changes for Single-Site Mutations Using Support Vector Machines, PROTEINS: Structure, Function, and Bioinformatics. 2006, 62:1125-1132) |
Structure image for HCN4 from PDB |
Top |
Differential gene expression and gene-gene network for HCN4 |
Differential gene expression between mutated and non-mutated LBS samples in all 16 major cancer types |
Differential co-expressed gene network based on protein-protein interaction data (CePIN) |
Top |
Top |
Phenotype information for HCN4 |
Gene level disease information (DisGeNet) |
Disease ID | Disease name | # PubMed | Association type |
umls:C1834144 | Sick Sinus Syndrome 2, Autosomal Dominant | 2 | Biomarker, GeneticVariation |
umls:C0004238 | Atrial Fibrillation | 1 | Biomarker |
Mutation level pathogenic information (ClinVar annotation) |
Allele ID | AA change | Clinical significance | Origin | Phenotype IDs |
Top |
Pharmacological information for HCN4 |
Gene expression profile of anticancer drug treated cell-lines (CCLE) Heatmap showing the correlation between gene expression and drug response across all the cell-lines. We chose the top 20 among 138 drugs.We used Pearson's correlation coefficient. |
Drug information targeting mutLBSgene (Approved drugs only) |
Drug status | DrugBank ID | Name | Type | Drug structure |
Gene-centered ligand-gene interaction network |
Ligands binding to mutated ligand binding site of HCN4 go to BioLip |
Ligand ID | Ligand short name | Ligand long name | PDB ID | PDB name | mutLBS | PCG | CYCLIC GMP | 4kl1 | A | F564 E566 F613 | PCG | CYCLIC GMP | 4kl1 | B | F564 E566 F613 | PCG | CYCLIC GMP | 4kl1 | C | F564 E566 F613 | PCG | CYCLIC GMP | 4kl1 | D | F564 E566 F613 | CMP | 3',5'-CYCLIC AMP | 3otf | A | R669 | CMP | 3',5'-CYCLIC AMP | 3u11 | B | R669 | 7CH | 7-CH-CAMP | (2S,4AR,6R,7R,7AS)-6-(4-AMINO-7H-PYRROLO[2,3- D]PYRIMIDIN-7-YL)TETRAHYDRO-4H-FURO[3,2-D][1,3, 2]DIOXAPHOSPHININE-2,7-DIOL 2-OXIDE | 4nvp | A | R669 | PCG | CYCLIC GMP | 4kl1 | A | R669 | PCG | CYCLIC GMP | 4kl1 | C | R669 | CMP | 3',5'-CYCLIC AMP | 3u11 | A | R669 R713 | CMP | 3',5'-CYCLIC AMP | 4hbn | A | R669 R713 | PCG | CYCLIC GMP | 4kl1 | B | R669 R713 | PCG | CYCLIC GMP | 4kl1 | D | R669 R713 |
Top |
Conservation information for LBS of HCN4 |
Multiple alignments for Q9Y3Q4 in multiple species |
LBS | AA sequence | # species | Species |
Copyright © 2016-Present - The University of Texas Health Science Center at Houston |